CN102015675B - 作为凝血因子Xa和凝血酶的抑制剂的氯噻吩-酰胺 - Google Patents

作为凝血因子Xa和凝血酶的抑制剂的氯噻吩-酰胺 Download PDF

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CN102015675B
CN102015675B CN200980114013.9A CN200980114013A CN102015675B CN 102015675 B CN102015675 B CN 102015675B CN 200980114013 A CN200980114013 A CN 200980114013A CN 102015675 B CN102015675 B CN 102015675B
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alkyl
alkylene
formula
mmol
fluoroalkyl
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CN102015675A (zh
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马库斯·福尔曼
沃尔克马·韦纳
杰罗姆·梅尼罗尔
让-米歇尔·阿尔滕伯格
弗雷德里克·佩蒂特
吉尔伯特·拉萨尔
让-帕斯卡尔·赫劳尔特
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Beijing Lianxin Pharmaceutical Co ltd
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Sanofi Aventis France
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D333/40—Thiophene-2-carboxylic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CN200980114013.9A 2008-02-21 2009-02-10 作为凝血因子Xa和凝血酶的抑制剂的氯噻吩-酰胺 Active CN102015675B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP08290279 2008-02-21
EP08290279.2 2008-02-21
PCT/EP2009/000903 WO2009103440A1 (en) 2008-02-21 2009-02-10 Chlorothiophene-amides as inhibitors of coagulation factors xa and thrombin

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CN102015675A CN102015675A (zh) 2011-04-13
CN102015675B true CN102015675B (zh) 2014-07-02

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US (1) US8378092B2 (https=)
EP (1) EP2254881B1 (https=)
JP (1) JP5422570B2 (https=)
CN (1) CN102015675B (https=)
AR (1) AR070441A1 (https=)
AU (1) AU2009217075B2 (https=)
CA (1) CA2714654A1 (https=)
CL (1) CL2009000367A1 (https=)
DK (1) DK2254881T3 (https=)
ES (1) ES2394550T3 (https=)
PA (1) PA8816101A1 (https=)
PE (1) PE20091729A1 (https=)
PT (1) PT2254881E (https=)
TW (1) TW200948366A (https=)
UY (1) UY31666A1 (https=)
WO (1) WO2009103440A1 (https=)

Families Citing this family (8)

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CN103732589B (zh) 2011-05-25 2016-03-30 百时美施贵宝公司 可用作抗细胞凋亡bcl抑制剂的取代的磺酰胺
CN102924442B (zh) * 2012-11-15 2014-10-29 沈阳药科大学 含有噻唑环的色满类化合物及其类似物和医药用途
WO2014174102A1 (en) * 2013-04-26 2014-10-30 Sanofi Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(s)-2-[methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl piperazin-1 -yl)-3-oxo-propryl]amide
CN104557928B (zh) * 2015-02-14 2016-08-24 佛山市赛维斯医药科技有限公司 一种含二环酰胺结构凝血因子Xa抑制剂、其制备方法及其用途
US9701671B2 (en) * 2015-02-20 2017-07-11 Canon Kabushiki Kaisha Organic compound, electrochromic element containing the same, optical filter, lens unit, imaging device, and window component
WO2017030987A1 (en) * 2015-08-14 2017-02-23 The Broad Institute, Inc. Compositions and methods for treating multiple myeloma
US20250002483A1 (en) * 2021-09-03 2025-01-02 Bayer Aktiengesellschaft Substituted s-alaninate derivatives
EP4669644A1 (en) 2023-02-21 2025-12-31 Bayer Aktiengesellschaft SUBSTITUTED S-ALANINATE DERIVATIVES

Citations (1)

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WO2004052851A1 (en) * 2002-12-06 2004-06-24 Glaxo Group Limited Pyrrolydin-2-one derivatives as inhibitors of thrombin and factor xa

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GB9322976D0 (en) * 1993-11-08 1994-01-05 Pfizer Ltd Therapeutic agents
US6313242B1 (en) * 1996-05-20 2001-11-06 Fina Technology, Inc. Stereorigid bis-fluorenyl metallocenes
JP2001512439A (ja) * 1997-02-06 2001-08-21 メルク エンド カンパニー インコーポレーテッド 線維素原受容体拮抗薬プロドラッグ
WO2000075129A1 (en) * 1999-06-07 2000-12-14 Shire Biochem Inc. Thiophene integrin inhibitors
WO2001038309A1 (en) 1999-11-24 2001-05-31 Cor Therapeutics, Inc. β-AMINO ACID-, ASPARTIC ACID- AND DIAMINOPROPIONIC-BASED INHIBITORS OF FACTOR Xa
CA2511500A1 (en) * 2002-12-24 2004-07-15 Daiichi Pharmaceutical Co., Ltd. Novel ethylenediamine derivatives
WO2007056056A2 (en) 2005-11-02 2007-05-18 Cytokinetics, Inc. Mitotic kinesin inhibitors

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WO2004052851A1 (en) * 2002-12-06 2004-06-24 Glaxo Group Limited Pyrrolydin-2-one derivatives as inhibitors of thrombin and factor xa

Non-Patent Citations (1)

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The Design and Synthesis of Thrombin Inhibitors: Analogues of MD805 Containing Non-Polar Surrogates for Arginine at the P1 Position;Urs Baettig,et al.;《Bioorganic & Medicinal Chemistry Letters》;20001231;第10卷;第1563-1566页 *

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CN102015675A (zh) 2011-04-13
WO2009103440A1 (en) 2009-08-27
CL2009000367A1 (es) 2009-06-26
PT2254881E (pt) 2012-12-10
AU2009217075B2 (en) 2013-05-16
AU2009217075A1 (en) 2009-08-27
EP2254881A1 (en) 2010-12-01
JP2011512368A (ja) 2011-04-21
EP2254881B1 (en) 2012-09-12
DK2254881T3 (da) 2012-12-10
PE20091729A1 (es) 2009-12-01
JP5422570B2 (ja) 2014-02-19
UY31666A1 (es) 2009-09-30
AR070441A1 (es) 2010-04-07
TW200948366A (en) 2009-12-01
PA8816101A1 (es) 2009-09-17
HK1156607A1 (en) 2012-06-15
ES2394550T3 (es) 2013-02-01
US8378092B2 (en) 2013-02-19
CA2714654A1 (en) 2009-08-27
US20110112075A1 (en) 2011-05-12

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